| ObjectiveThrough the network meta-analysis and systematic review,we compared and ranked the comparative effectiveness and safety of the Chinese herb medicine(CHM)extracts combined with methotrexate(MTX)and/ or leflunomide(LEF)for rheumatoid arthritis(RA),to provide the reference comments in the choice of the clinical treatment options.MethodsThe following databases were searched: China National Knowledge Infrastructure(CNKI),Chinese Biomedical Database(CBM),Chinese Scientific Journal Database(CQVIP),Wanfang Database,Chinese Clinical Guideline Library.The beginning and ending date of searching was from the inceptions of these databases to June 21 st 2017.The clinical guideline about Chinese medicine treatment of RA were collected in the round.The relative CHM extracts were wrote up.And After have discussed with the clinicians of the Rheumatoid Department about the practical use of the CHM extracts,those Chinese medicine used commonly in the practice were compared by the network meta-analysis.The searched Chinese and English medicine databases include CBM,CNKI,Wanfang,CQVIP,PubMed,The Cochrane Central Register of Controlled Trials(CENTRAL),EMbase.The retrieval time dates from the beginning of the databases to August30 th 2017.The randomized controlled trials(RCTs)about Chinese medicine treatment of RA were gathered comprehensively.Data extraction that performed through the use of Epidata and the risk of the bias of the eligible studies were assessed by risk of bias tool of Cochrane handbook 5.1.0.In the end,the Stata 13.1 was used for the graghs of the evidence relation optioned from the network meta-analysis and the statistical heterogeneity of the closed ring.WinBUGS1.4.3 and the gemtc package of R software were used to conduct the node analysis to exam the homogeneity,verify the fit degree of the model,analyzeand rank the statistical results and so on.ResultsAfter have finished retrieval,10 guidelines and 5 medicine books about Chinese medicine treatment of RA are fit into the study,which involve 20 kinds of CHM extracts.The conclusion was drawn from the discussion with the clinicians of the Rheumatoid Department that the CHM extracts practiced commonly was included in Network meta-analysis.And these extracts included TG(TG),TGP(TGP),Sinomenine(SN),Kunxian capsule(KXC),Biqi capsules(BQC),Wangbi tablets,Yishenjuanbi pills.35 RCTs about CHM extracts for RA were eligibled.Through the direct comparison meta-analysis and the network Meta-analysis,the results showed that:(1)ACR20: The 18 studies fit into the research contained 12 interventions.The result from the direct comparison meta-analysis reflected: TGP + MTX VS MTX(OR=3.63,95%CI[1.08,12.18]),Kunxian capsule + MTX VS MTX(OR=3.10,95%CI[1.57,6.12]),LEF VS MTX(OR=3.63,95%CI[1.08,12.18]),TG +MTX VS MTX+LEF(OR=0.50,95%CI[0.26,0.94]),MTX VS MTX+LEF(OR=0.07,95%CI[0.01,0.52]).It had the statistical significance.The result of the network meta-analysis reflected: MTX+LEF VS MTX(OR=10.07,95%CrI[2.98,31.99]),TGP+MTX+LEF VS MTX(OR=18.73,95%CrI[3.63,98.11]),Kunxian capsule+MTX VS MTX(OR=3.15,95%CrI[1.07,9.07]),TG+MTX VS MTX(OR=4.61,95%CrI[1.74,11.54]),Sinomenine+MTX+LEF VS MTX(OR=28.91,95%CrI[3.23,291.58]),Sinomenine+ MTX VS TGP+MTX+LEF(OR=0.12,95%CrI[0.02,0.93]),Sinomenine+MTX+LEF VS Sinomenine+MTX(OR=12.55,95%CrI[1.09,163.68]),It had the statistical significance.The rank of the effectiveness of the 12 interventions was: Sinomenine+MTX+LEF;TGP+MTX+LEF;MTX+LEF;TGP+LEF;TG + MTX;TGP+MTX;LEF;Yishenjuanbi pills +MTX;Kunxian capsules + MTX;Biqi capsules + MTX;Sinomenine+MTX;MTX.(2)ACR50: The 15 studies included into the research involved 12 interventions.The result from the direct comparison meta-analysis reflected: TGP+MTX VS MTX(OR=2.11,95%CI[1.12,3.97]),TGP+LEF VS LEF(OR=3.44,95%CI[1.10,10.78]),Kunxian capsules + MTX VS MTX(OR=2.05,95%CI[1.19,3.54]),TG + MTX VS MTX(OR=3.21,95%CI[1.82,5.65]),TG + MTX VS MTX+LEF(OR=0.47,95%CI[0.28,0.79]),Sinomenine+MTX+LEF VS MTX+LEF(OR=4.00,95%CI[1.37,11.70]),Sinomenine+MTX VS MTX(OR=2.12,95%CI[1.13,4.35]),MTX VS MTX+LEF(OR=0.31,95%CI[0.12,0.80]).The result had statistical significance.The result of the network meta-analysis showed that: MTX+LEF VS MTX(OR=6.19,95%CrI[2.48,14.95]),TGP+ MTX VS MTX(OR=2.54,95%CrI[1.13,5.43]),TGP + LEF VS MTX(OR=10.94,95%CrI[1.77,63.46]),TGP + MTX + LEF VS MTX(OR=9.84,95%CrI[2.65,32.71]),TG + MTX VS MTX(OR=3.22,95%CrI[1.44,7.17]),Sinomenine+ LEF + MTX VS MTX(OR=25.60,95%CrI[5.06,125.81]),Sinomenine + LEF + MTX VS LEF(OR=8.50,95%CrI[1.44,53.52]),Sinomenine+ LEF+ MTX VS LEF + MTX(OR=4.13,95%CrI[1.11,17.22]),Sinomenine + LEF + MTX VS TGP+ MTX(OR=10.15,95%CrI[1.88,55.73]),Sinomenine + LEF + MTX VS Kunxian capsules+ MTX(OR=12.49,95%CrI[2.12,75.23]),Sinomenine+ LEF + MTX VS TG +MTX(OR=7.97,95%CrI [1.83,36.47]),Sinomenine + LEF + MTX VS Yishenjuanbi pills+ MTX(OR= 16.04,95%CrI[2.16,119.14]),Sinomenine + LEF + MTX VS Sinomenine +MTX(OR=11.45,95%CrI[1.85,69.72]),TGP + MTX + LEF VS TGP +MTX(OR=3.99,95%CrI[1.04,14.75]).The rank of the effectiveness of the 11 interventions was:Sinomenine + LEF + MTX;TGP + LEF;TGP + MTX + LEF;MTX +LEF;TGP + MTX;LEF;TG + MTX;Sinomenine + MTX;Kunxian capsules + MTX;Yishenjuanbi pills + MTX;MTX.(3)ACR70: The 10 studies included into the research involved 10 interventions.The result from the direct comparison meta-analysis reflects:(OR=2.90,95%CI[1.19,7.07]),Biqi capsules + MTX VS MTX(OR=2.46,95%CI[1.23,4.92]),Kunxian capsules + MTX VS MTX(OR=3.82,95%CI[1.15,12.71]),TG + MTX VS MTX(OR=2.60,95%CI[1.47,4.59]),MTX VS MTX + LEF(OR=0.23,95%CI[0.10,0.56]).It had statistical significance.The result of the network meta-analysis showed that:(OR=4.58,95%CrI[1.59,13.58]),TGP + MTX + LEF VS MTX(OR=6.37,95%CrI[1.46,27.02]),Biqi capsules + MTX VS MTX(OR=2.67,95%CrI[1.02,6.89]),TG + MTX VS MTX(OR=2.60,95%CrI[1.09,6.22]),Sinomenine + LEF + MTX VS MTX(OR=9.37,95%CrI[1.38,73.99]).It had statistical significance.The rank of the effectiveness of the 10 interventions was: Sinomenine + LEF + MTX;TGP + MTX + LEF;MTX + LEF;Kunxian capsules + MTX;TGP + LEF;TGP + MTX;Biqi capsules + MTX;TG + MTX;LEF;MTX.(4)DAS28: There were few of the studies reported the DAS28,so it was unable to perform the network Meta-analysis.Consequently,the random effect model was adopted to conduct the direct comparison meta-analysis.The result showed that: TGP + LEF VS LEF(SMD=-0.33,95%CI [-0.64,-0.01]),Kunxian capsules +MTX VS MTX(SMD=-0.72,95%CI [-1.25,-0.1]),Sinomenine + MTX VS MTX(SMD=-0.59,95%CI [-0.79,-0.39]).It had statistical significance.(5)In the aspect of safety evaluation,the 17 studies included into the research.The result from the direct comparison meta-analysis reflected: TGP+MTX+LEF VSMTX+LEF(OR=0.29,95%CI[0.14,0.58])had statistical significance.ConclusionsACR: The results of the direct comparison meta-analysis and the network meta-analysis showed that the effectiveness of the CHM extracts combined with MTX and LEF in the treatment group were superior to the one of the therapeutic in the control group.And the ranks of the effect of every intervention were about the same.The top three were:Sinomenine + LEF + MTX;TGP + MTX + LEF;MTX + LEF.DAS28: The treatment groups of TGP+LEF was better than the LEF group;Kunxian capsules + MTX and Sinomenine + MTX is better than the MTX group.In the aspect of safety evaluation,the treatment measures of TGP+MTX+LEF were lower than those of MTX combined with LEF in the incidence of adverse reactions.The other interventions had no statistically significant difference in the incidence of adverse reactions compared with the control group.However,for every intervention,the number of the eligible studies were relatively less and the methodological quality of the research included in the studies were quite weak.Therefore,in practice,the clinicians were needed to exercise caution over using this evidence to make clinical decision.It is necessary that further research were performed through the clinical trials with high methodological quality and large sample size. |
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